Ampk activator screening

The discrepancies as illustrated in the biological assays emphasized the necessity of using both AMPK kinase assay and cell-based AMPK phosphorylation assessments for validating newly discovered AMPK modulators, which are important procedures in the proposed method.

This is further supported by the observation that there is no direct correlation between the binding energy and the activity of the tested compounds. The proposed constituting biological assays are useful for providing experimental data to compensate the crude in silico prediction for the activity of the tested compounds acquired from the first docking step.

The molecular function of some patented anilides and their derivatives or analogs are associated with the inhibition of kinase in the Rho and Src families Feng et al. To our knowledge this is the first example demonstrating the capability of anilide-based compounds of functioning as direct AMPK modulators which may suggest new mechanism of action for explaining the pharmacological effects of these compounds.

The chemical structures of the identified compounds were subjected to in-depth analysis. Most of them were found to have their anilides or anilide-like nucleus linked to the proton acceptors.

This notion was supported by the fact that, more than half c. The result acquired from the detailed docking analysis of compound a are in line with these findings as well.

The virtual screening suggested that the proton acceptor structures of a can potentially interact with AMPK at the binding pocket mediated by H-bond formation, which, together with other hydrophobic, polar, and electrostatic interactions between other side chains of a and AMPK, may most probably contribute to the proper positioning of a within the binding pocket.

Such observation may provide insight to the development of AMPK modulators with desired pharmacological performance through suitable structural modification of compounds in the anilide group. It is important to have a brief idea of the oral bioavailability of a newly found compound for referencing the likelihood of further large scale and intensive in vivo assessments. In the current study, we have figured out from the 17 compounds, 12 of them were having the potential to reach the systemic circulation via oral administration.

These findings was acquired in 4 months commenced with the virtual screening of over a million of compounds from the database which highlighted the efficacy and practicality of the proposed method. We have proposed an efficient method, including the use of computational docking and straightforward biological methods, for the search of AMPK modulators from chemical database.

In addition, positioning of H-bond within these chemical structures determined the mechanism of actions of such compounds providing insight to drug synthesis via structural modifications. SM drafted the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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